Dopamine receptor agonists/antagonists are considered strong candidates for the treatment of cocaine addiction. However, as cocaine is likely to be used with other drugs, including marijuana, we investigated whether dopamine agonists modify the behavioral effects of cannabinoids in monkeys. The cannabinoid agonist l-nantradol was studied alone to establish a dose response relationship. High doses of l-nantradol reduced activity and induced sedation. For each subject, a dose of l-nantradol that did not produce sedation or reduced activity when administered was identified. This subthreshold dose was administered along with a full range of doses of the D2/D3 dopamine receptor agonist quinelorane. Paradoxically, this drug combination produced significant decreases in motor activity, general activity and marked sedation. These effects are unanticipated because D2/D3 agonists generally stimulate motor and other activity in nonhuman primates. These results indicate cannabinoid and dopamine agonist interactions warrant further investigation in light of the